Clinical significance of dihydropyrimidine dehydrogenase in adjuvant 5-fluorouracil liver perfusion chemotherapy for pancreatic cancer

Abstract

Objective: To clarify the relationship between intratumoral dihydropyrimidine dehydrogenase (DPD) expression and response to 5-fluorouracil (5-FU) liver perfusion chemotherapy (LPC) in pancreatic cancer patients, we evaluated DPD expression immunohistochemically in resected pancreatic cancer tissues.

Summary background data: Pancreatic cancer is considered a disease with a poor prognosis even if aggressive resection is performed. One of the main causes of death is hepatic metastasis soon after surgery. As a treatment, we have assessed adjuvant LPC via the portal vein using 5-FU just after pancreatectomy for advanced pancreatic cancer since 1994. However, the results remain unsatisfying.

Methods: Sixty-eight resected specimens were obtained from patients with pancreatic cancer from 1988 to 2000. Formalin-fixed paraffin-embedded tissues were immunostained with polyclonal anti-DPD antibody. The relation between intratumoral DPD expression and the prognoses of pancreatic cancer patients was investigated statistically.

Results: Of the 68 tumors studied, 27 carcinomas (39.7%) were DPD(+), and 41 (60.3%) were DPD(-). In the DPD(+) group, there was no significant difference between the LPC(+) and LPC(-) subgroups, whereas in the DPD(-) group the LPC(+) subgroup showed a significantly higher survival rate than the LPC(-) subgroup. Moreover, in the LPC(+) group, overall survival in the DPD(-) subgroup was significantly better than in the DPD(+) subgroup.

Conclusions: An immunohistochemical evaluation of intratumoral DPD expression might be useful in predicting responsiveness to 5-FU-based chemotherapy in pancreatic cancer patients. In the DPD(-) group, liver perfusion chemotherapy using 5-FU via the portal vein is effective adjuvant therapy for pancreatic cancer once pancreatectomy has been performed.

FIGURE 1. Immunohistochemical staining for DPD. A, DPD(+) moderately-differentiated adenocarcinoma. B, DPD(+) poorly-differentiated adenocarcinoma.

FIGURE 2. Overall survival by LPC in stages II, III, and IV. A, In DPD(−) group, LPC(+) subgroup showed significantly better survival than LPC(−) subgroup. B, In DPD(+) group, there was no significant difference between LPC(+) and LPC(−) subgroups.

FIGURE 3. Overall survival by DPD expression in stages II, III, and IV. A, In LPC(+) group, DPD(−) subgroup showed significantly better survival than DPD(+) subgroup. B, In LPC(−) group, there was no significant difference between DPD(−) and DPD(+) subgroups.